There have conventionally been several methods for producing (R)-2-amino-1-phenylethanol or its halogen substitution products, represented by Formula (2). The following methods for producing optically active 2-amino-1-phenylethanol or its halogen substitution products are known:
(1) optical resolution by lipase (J. Chem. Soc. Perkin Trans., 1, 1759-1762 (1992)); PA1 (2) preparing (R)-mandelonitrile by (R)-oxynitrilase, and then reducing it using LiAlH.sub.4 (Synthesis, (7), 575-578 (1990)); PA1 (3) asymmetrically reducing .alpha.-chloroacetophenon using bakers' yeast, and then aminating the product (Indian J. Chem., Sect. B, 31B(12), 821-823 (1992)); PA1 (4) aminating an optically active styrene oxide (Japanese Patent Laid-Open Publication No. Sho 61-85197); PA1 (5) selectively crystallizing the (R)-form of a 3-amino benzoate (Nippon Kagaku Kaishi (5), 910-913 (1985)); PA1 (6) asymmetrically reducing benzoyl cyanide with the presence of alpine borane to obtain the R form (J. Org. Chem., 50, 3237-3239 (1985)); PA1 (7) asymmetrically reducing in the presence of a catalyst of binaphthyl phosphine substituting an alkali metal sulfonate (Japanese Patent Laid-Open Publication No. Hei 5-170780). PA1 (8) mixing a solution of N-(t-butoxycarbonyl)-D-alanine and a solution of racemic 2-amino-1-(3-chlorophenyl)ethanol, forming a salt of diasteroisomers, and then optically resolving the salt by means of preferentially crystallizing a salt of (R)-2-amino-1-(3-chlorophenyl)ethanol and N-(t-butoxycarbonyl)-D-alanine (European Patent Laid-Open Publication No. 294995). PA1 (9) performing aldol condensation of 2-formyl-3-hydroxy2.2!para-cyclophane (Angew. Chem., 106 (1), 106-108 1994)); PA1 (10) performing aldol condensation using aldolase, or conversely treating a racemate with aldolase and leaving an enantiomer (Japanese Patent Laid-Open Publications No. Hei 6-165693 and No. Hei 6-125786; Japanese Patent Publication No. Sho 52-46313; Can. J. Chem., 72 (1), 114-117 (1994)); PA1 (11) using an artificial enzyme comprising a lipid having (S)-binaphthol and (S)-alanine, a pyridoxal derivative, and Cu(II) (Chem. Lett., (1), 55-58 (1994)); PA1 (12) optically resolving an N-phenylacetylated derivative using penicillin acylase (Bioorg. Khim., 19 (4), 478-483 (1993)); PA1 (13) using serine hydroxymethyl transferase (Tetrahedron, 48(12), 2507-2514 (1992)); PA1 (14) brominating an N-phthaloyl-.alpha.-amino acid ester using N-bromosuccinimide, and then reacting with AgNO.sub.3 (Tetrahedron Lett., 31 (48), 7059-7062 (1990)); PA1 (15) condensing an isocyanocarboxylic acid and an aldehyde in the presence of an optically active ferrocene and a gold complex to form an optically active oxazoline, and then hydrolyzing the optically active oxazoline (Japanese Patent Laid-Open Publication No. Sho 63-60977); PA1 (16) performing aldol condensation of an aldehyde and a Ni(II) complex of a Schiff base derived from (S)-o-N-(N-benzylprolyl)amino!benzophenone and glycine (J. Chem. Soc. Perkin Trans. 1 (24), 3143-3155 (1993)). PA1 In Method (1), the enzyme used is expensive, the separation of the product is not easy, and the yield is not high. PA1 Also, in Method (2), the enzyme used is expensive, and is required at a high concentration of 10,000 U/l. PA1 In Method (3), both reaction yield and substrate concentration are low. PA1 In Method (4), the amount of optically active ethylene oxide produced by the microbial reaction is very small, resulting in high cost. PA1 In Method (5), the solubility of the benzoate is low, and the amount of crystals obtained in one batch is small, which is not economical. PA1 In Method (6), the alpine borane is expensive, and its optical purity is not sufficiently high. PA1 In Method (7), the binaphthyl phosphine catalyst is very expensive. PA1 In Method (8), very expensive N-Boc-D-alanine requires an efficient recovering method, which precludes it from industrial use. PA1 In Methods (9), (11), (15), and (16), a large amount of an optically active catalyst needs to be synthesized. Difficulty and high cost accompany this synthesis. Therefore, these methods are not practical. The configuration of two successive asymmetric centers cannot be completely controlled. Consequently, the product must be further purified by other means such as column chromatography. In addition, this reaction occasionally requires a very low temperature of -80.degree. C. PA1 In Methods (10) and (13), the concentration of the obtained product is low, and an aldehyde used may cause the inactivation of the enzyme. In these synthesizing reactions, the configuration at the 3 position cannot be controlled. PA1 In Method (12), the enzyme itself is expensive. PA1 In Method (14), the ratio of (2S, 3R)-form to (2S, 3S)-form is 5:1. The stereoselectivity is not satisfactory, and furthermore the reaction requires multiple steps. PA1 Preventing oxygen from being in contact with the reaction mixture by replacing the gas over the reaction mixture with nitrogen, or sealing the reaction fluid by placing liquid paraffin on the top surface, may lead to a preferable result. The reaction is usually carried out in the temperature range of 5.degree. to 70.degree. C., preferably 20.degree. to 40.degree. C. for the genuses Lactobacillus and Providencia, 45.degree. to 60.degree. C. for the genuses Enterococcus, Gibberella and Fusarium, and 25.degree. to 60.degree. C. for tyrosine decarboxylase. The pH of the reaction mixture is appropriately set at a value in the range where the enzyme can decarboxylate the substrate. The pH is usually maintained at 4 to 11, preferably 5 to 9 with a buffered solution or pH-stat. The reaction can be performed under static, shaken, or stirred conditions. The solvent used for the reaction is usually water. An organic solvent such as alcohol can be added as long as its addition does not adversely affect the reaction. The produced (R)-2-amino-1-phenylethanol or its halogen substitution products can be collected and purified by a combination of conventional methods, such as ultrafiltration, concentration, column chromatography, extraction, and crystallization. The remaining optically active threo-3-phenylserine or its halogen substitution products can be collected and purified by a similar method. PA1 Microorganism culture medium 1A: mixing 5 g of glucose, 5 g of yeast extract (Kyokuto Pharmaceutical Industrial Co., Ltd.), 5 g of polypeptone (Nihon Seiyaku Co., Ltd.), 1 g of MgSO.sub.4 7H.sub.2 O, 0.2 g of DL-threo-3-(3-chlorophenyl)serine and 0.1 g of pyridoxal hydrochloride, bringing the total volume up to 1000 ml with deionized water, and adjusting the pH to 7.0. PA1 Microorganism culture medium 1B: mixing 5 g of glucose, 5 g of yeast extract (Kyokuto Pharmaceutical Industrial Co., Ltd.), 5 g of polypeptone (Nihon Seiyaku Co., Ltd.), 1 g of MgSO.sub.4 7H.sub.2 O, 0.2 g of L-tyrosine and 0.1 g of pyridoxal hydrochloride, bringing the total volume up to 1000 ml with deionized water, and adjusting the pH to 7.0. PA1 Microorganism culture medium 2: mixing 5 g of glucose, 0.7 g of KH.sub.2 PO.sub.4, 1.3 g of (NH.sub.4).sub.2 PO.sub.4, 0.5 g of MgSO.sub.4 7H.sub.2 O, 3 g of yeast extract (Kyokuto Pharmaceutical Industrial Co., Ltd.), 5 g of polypeptone (Nihon Seiyaku Co., Ltd.) and 0.2 g of DL-threo-3-(3-chlorophenyl)serine, bringing the total volume up to 1000 ml with deionized water, and adjusting the pH to 7.2. PA1 Microorganism culture medium 3: mixing 20 of glycerin, 3 g of yeast extract (Kyokuto Pharmaceutical Industrial Co., Ltd.), 5 g of polypeptone (Nihon Seiyaku Co., Ltd.), 3 g of malt extract (Kyokuto Pharmaceutical Industrial Co., Ltd.), 0.1 g of pyridoxal hydrochloride and 1000 ml of deionized water, and adjusting the pH to 7.0. PA1 Microorganism culture medium 4: mixing 5 g of glycerin, potato extract from 200 g of potato (prepared by cutting 200 g of peeled potato into 1-cm cubes, boiling them in 1000 ml of added water for 20 min, and then filtering with gauze) and 0.1 g of pyridoxal hydrochloride, bringing the total volume up to 1000 ml with deionized water, and adjusting the pH to 5.6. PA1 Microorganism culture medium 5: mixing 24 g of glucose, 19.2 g of yeast extract (Asahi Breweries, Ltd.), 1.3 g of KH.sub.2 PO.sub.4, 2.4 g of (NH.sub.4).sub.2 SO.sub.4 7H.sub.2 O, 1.3 g of MgSO.sub.4.7H.sub.2 O, 0.016 g of FeSO.sub.4 7H.sub.2 O, 0.016 g of ZnSO.sub.4 7H.sub.2 O and 0.3 g of FS anti-foam 028 (Dow Corning Inc.), bringing the total volume up to 1000 ml with deionized water, and adjusting the pH to 6.0. PA1 YM medium: 10 g of glucose, 3 g of yeast extract (Kyokuto Pharmaceutical Industrial Co., Ltd.), 3 g of malt extract (Kyokuto Pharmaceutical Industrial Co., Ltd.) and 5 g of polypeptone (Nihon Seiyaku Co., Ltd.), bringing the total volume up to 1000 ml with deionized water, and adjusting the pH to 6.0.
The following method for producing (R)-2-amino-1-(3-chlorophenyl)ethanol is the only method known:
The following methods for producing optically active phenylserine and its halogen substitution products are known:
With regard to 3-(3-chlorophenyl) serine, a substrate of the reaction used in the present invention, its erythro form has been reported (R. J. Ulevitch and R. G. Kallen, Biochemistry, 16 (24), 5355-5363 (1977)), but no detailed synthesizing method is described.
The conventional methods for producing (R)-2-amino-1-phenylethanol or its halogen substitution products, have the following problems:
As described above, the conventional methods cannot realize industrial and economical production of (R)-2-amino-1-phenylethanol and its halogen substitution products, represented by Formula (2). Therefore, there is a desire to develop a method for producing (R)-2-amino-1-phenylethanol and its halogen substitution products, which can be industrially employed.
The conventional methods for producing optically active phenylserine and its halogen substitution products, have the following problems:
As shown above, the conventional methods do not enable industrial economical production of optically active phenylserine and its halogen substitution products.
Tyrosine decarboxylase (EC 4.1.1.25) exists in microorganisms, and is known as an enzyme which catalyzes the reaction converting L-tyrosine into tyramine. Pyridoxal-5'-phosphate is a coenzyme of this enzyme (E. A. Boeker and E. E. Snell, "The Enzyme" Vol. 6, pp. 217-253, Academic Press, New York (1972)). The activity of tyrosine carboxylase is observed in the genuses Latobacillus, Pseudomonas, and Enterococcus. Especially, Enterococcus faecalis is widely known to have high activity. Several studies of the substrate specificity of these enzymes have been reported. In most of them, substrates in which the hydrogen atom of the phenyl group in tyrosine molecules is replaced at the para position, or at the para and meta positions, are investigated (for example, R. Ferrini and A. Glasser, Biochem. Pharmacol., 13, 798-801 (1964)). No substrate in which the hydrogen atom is replaced with a hydroxyl group at the .beta. position has been investigated at all. Japanese Patent Publication No. Sho 52-31428 discloses that an aromatic amino acid decarboxylase derived from microorganisms of the genus Micrococcus, slightly acts on DL-3-phenylserine. However, neither the optical purity nor accurate concentration of the product is described. A microorganism of the genus Fusarium has been reported to have the activity of phenylalanine decarboxylase (M. Ferencik and K. Ladzianska, Folia Microbiology, 13, 414-418 (1968)). However, it has not been clarified what species has the activity of phenylalanine decarboxylase, nor is it described whether the microorganism acts on a substrate provided by the present invention. No investigations have been reported as to whether a microorganism of the genus Gibberella has the activity of an amino acid decarboxylase.
Thus, the following matters have not been known: Tyrosine decarboxylase, or microorganisms of the genuses Enterococcus, Lactobacillus, Providencia, Fusarium, and Gibberella act on enantiomer mixtures of threo-3-phenylserine or its halogen substitution products to produce (R)-2-amino-1-phenylethanol or its halogen substitution products. At the same time, one of the enantiomers of threo-3-phenylserine or its halogen substitution products is selectively left to produce optically active threo-3-phenylserine or its halogen substitution products.